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1 BI 3010 H08 Population Genetics Halliburton Chapter 4-5 Recombinations: Any process which creates new combinations (genotypes) of existing alleles in the offspring from sexual reproductions. Recombinations come from crossing overs during meiosis pro-phase 1. Unlike for mutations, no new genetic material is formed; instead there is a "re-use" of existing variant genes. Nonetheless, the offspring can possess new phenotypic traits that were not present in any of the parents. Linkage: Two loci are linked if they are localized sufficiently near each other on the same chromsome, so that the recombination frequency is < 50%. Linked loci thus tend to be inherited together (i.e. in the same gamete). D = gametic (linkage) disequilibrium: For example HW-equilibrium at each of two loci, but non-random distribution of locus-1 genotypes among locus-2 genotypes. This can be brought about by any of the four evolutionary forces. If the responsible evolutionary force is relaxed, D will be reduced by time (generations). For a recombination frequency of 0.5, D approaches zero after 7-8 generations. D t = (1-r) t D 0

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2 BI 3010 H08 Genetic identification: In forensics it can be crucial to be able to link a perpetrator to the crime scene. Traditionally, fingerprinting has been the method of choise. However, molecular genetic techniques (blood types, isozymes, DNA) have been increasingly used in the last decades ("Jeffrey's probes" for minisatellites"). The basis for these methods is the knowledge of the frequencies of different alleles in the population, an assumption that the loci used are not linked, and that the loci have many alleles (and thus many possible genotypes). In order to increase the statistical power of the conclusions, many polymorphic loci must be used. A multi- which frequency in the reference locus genotype (a "genetic profile") is established, which frequency in the reference population is the product of the frequencies of each single locus genotype. If each single locus genotype is rare due to the presence of many alleles at that locus, a multilocus profile can easily be extremely rare. In forensics genetics, so many loci are used that the probability of a "match" in the reference group by pure chance becomes extremely low, even in mankind as a whole. The development of DNA techniques has offered an enormous pool of allele-rich microsatellite loci for use in forensic laboratories. Tests of fatherhood are based on the same principles and techniques, and are equally extremely reliable. Population Genetics Halliburton Chapter 4-5

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6 BI 3010 H08 The binomial distribution describes the distribution of outcomes from n independent trials where each trial has two possible outcomes. Let the probability of one outcome (success) be p, and for the other (failure) 1-p. Further, let X be a random variable which denotes the number of successes in n trials. Hence, X can take the values 1,2,3,...n. The binomial distribution describes the probability (Pr) for each of the possible outcomes (i.e. number of successes in n trials). If x symbols one specific outcome for X, then Pr(X=x) = [ n! / (x!(n-x)! ] [ p x (1-p) n-x ] ( remember: 0! =1, and 1 0 = 1 ) Example: The probability of obtaining a "1" when throwing a dice once is 1/6. The probability to get exactly two "1"s (x=2) in five trials (n=5) is then: Pr(X=2) = [5! / 2!3!] [ (1/6) 2 (5/6) 3 ] = 0.16 Population Genetics Halliburton Chapter 4-5

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12 Natural selection I Basic models Evolution can be caused by several of the 4 evolutionary forces, either single or in concert. Selection is only one of them. Natural selection works on phenotypes. For selection to be an evolutionary force (cf Darwins' theory), three prerequisites must be fulfilled: 1. There must be phenotypic variation between the individuals in a population 2. The variation must result in individual fitness differences (survival, reproduction success) 3. The variation must, at least partly, be heritable (i.e. have a genetic basis) In population genetics, the term relative fitness denotes indidual genotypic performance relative to other genotypes on the same polymorphic locus (or for the same polymorphic loci for multi- locus traits). An example of how to calculate relative fitness for 2 traits can be found in Table 5.1 on page 131 in Halliburton. Fitness coefficient (w): The relative fitness of a genotype compared to the fitness of the best genotype is denoted by w, which value is fraction between 0 and 1. Selection coefficient (s): Defined as [ 1 – w ]. E.g.; if w=0.8, then s = 0.2. Population Genetics Halliburton Chapter 4-5 BI 3010 H08

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14 BI 3010 H08 Population Genetics Halliburton Chapter 4-5 The efficiency of selection, measured as the change in allele frequency per generation, depends not only on the size of the selection coefficients, but also on the allele frequency itself (the change per genaration is largest for allele frequencies around 0.5). This can be seen from the formula for the average fitness for the population for a single locus trait, where the allele frequencies are incorporated as follows: W mean = p 2 W FF + 2pq W FS + q 2 W SS From this formula we can (under some heroic assumptions) derive the "mean fitness" for each allele as: W F-mean = p W FF + q W FS, and W S-mean = p W FS + q W SS After some algebra the above formulas can be combined to give  p ; the change in allele frequency per generation due to selection:  p = pq [W F-mean – W S-mean ] / W mean which states that the speed of change in allele frequency per generation is proportional to the frequency ( pq ) of heterozygotes, which in turn is largest at allele frequencies around 0.5. At extreme allele frequencies (approaching 0 or 1), the change per generation will be small.

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16 Is the fitness of natural populations increasing? Populations adapt genetically to their environments, i.e. the allele frequencies change by time. The change in allele frequency (Δp) is related to the relative fitness value of alleles and the mean relative fitness coefficient of the population): Directional selection will allway increase the mean fitness of a population. With over- and underdominance the frequency of the favoured allele will change in a direction that increases the mean fitness. However, natural selection forces are probably not constant over time, life stages and seasons, and even not between sexes. It has been suggested that many of the polymorphisms that can be seen today are maintained by shifting selection regimes. There is also reason to emphasize the difference between absolute and relative fitness. The relative fitness of a certain genotype may increase evem if the absolute fitness of the population as a whole decreases (e.g. due to poorer life conditions). BI 3010 H08 Population Genetics Halliburton Chapter 4-5 See also formulae on slides 14 and 17

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18 The 3 main types of selection 1. Directional selection (heterozygote fitness intermedate between homozygotes) 2. Balanced polymorphism (heterozygot superiority, overdominance) 3. Disruptive selection (heterozygote inferiority; its w is lower than both homozyg.) Directional selection and disruptive selection will, after some time, lead to fixation of one allele and loss of the others, i.e reduction of genetic variability. Artificial selection (breeding) for productivity or exteriour traits works through selecting individuals with the preferred traits to be parents for the next generation. The traits are usually quantitative, like growth, age at maturity, disease resistence. Efficient breeding regimes will effectively change allele frequencies by directional selection. Again, this leads to loss of genetic variability. Natural selection for single-locus characters is excellently demonstrated by the so-called "industrial melanism" in the peppered moth (Biston betularia) in England, and the so-called sickle cell anemia in man (se Halliburton chap. 5.3 and 5.4). While the selection type in the moth resembles directional (or frequency-dependent), the sickle-cell anemia in Homo sapiens in regions with malaria is a classical example of a balanced polymorphism. BI 3010 H08 Population Genetics Halliburton Chapter 4-5

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20 During the period when the number of coal-burning factories in England was increasing (during the so-called Industrial Revolution) it was noticed that the number of melanic individuals of the species of Peppered Moth (Biston betularia) was becoming more common. Originally rare in the population of normally light-colored moths, the frequency of the melanic form increased in polluted areas until it was over 90%. This change in color has come to be known as "industrial melanism." "Industrial melanism" BI 3010 H08 Population Genetics Halliburton Chapter 4-5

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21 BI 3010 H08 Population Genetics Halliburton Chapter 4-5

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22 BI 3010 H08 Population Genetics Halliburton Chapter 4-5 Formulae for fitnesses and equilibrium allele frequency values are often more simple if we use allelic fitnesses rather than genotypic fitnesses, as shown in the box on the left.

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23 Sewall Wright’s shifting balance theory and adaptive landscapes: Sewald Wright formulated in 1932 the theory on "adaptive landscapes" of peaks and valleys, where the peaks represented points of maximal fitness. As evolution and selection always works to increase fitness, a population can be ”trapped” on a local peak (i.e. trapped at a certain allele frequency and genotypic composition). To escape such a peak and continue the fitness increas, natural selection would have to relax its strive towards increasing fitness, and allow the population to cross valleys lower fitness. However this will not happen, so the populations may never reach a global fitness maximum (see Halliburton Chapter 5.9 and 5.10). Ronald Fisher's fundamentale teorem om naturlig seleksjon: The rate of increase in a population’s fitness is proportional to the population’s variance for fitness. Components of fitness: Many components works together to shape an individual fitness; the fertility Of mother and father, fecundity of mother, survival, age at sexual maturation, mating ability of parents, number of offspring etc. A model for calculating of fitness coefficients can be very simple if focusing on only one fitness component, e.g. survival until reproduction (next slide). BI 3010 H08 Population Genetics Halliburton Chapter 4-5

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24 Eugenics ("racial hygienics") Between World War I and II, eugenics had considerable support (much more than we like to acknowledge) in Europe as well as in the USA. The background was in part the discovery that many human diseases (e.g. the bleeder disease) were heritable and surface under certain circumstances. The frequencies of deleterious recessive alleles are usually low, but increased homozygosity can arise from mating of close relatives. Actually, it is now known that each human is heterozygous for in average 8 alleles which can be lethal in double dose, or cause certain physical or mental diseases. From here, the idea that such diseases could be controlled by preventing certain individuals from reproducing, evolved into a more general eugenic thinking including races in humans. Many researchers made themselves spokesmen for the eradication of bad alleles through strict human breeding programs. Adolf Hitler incorporated this in his nazi ideology. However, these ideas were not based on sound population genetics theory. It is a fact that the harmful alleles ”hide” in heterozygotes which can be without symptoms. It can easily be shown that the eradication of harmful alleles in a population is a hopelessly ineffective exercise, since the frequency of heterozygotes is so much larger than the frequency of the double recessive ("visible") homozygotes. The course of a eradication process can easily be simulated with the computer program PopG.exe (uploaded to It’s learning), setting the fitness of one of the homozygotes to zero and the population size to e.g (cf next slide). Eugenics has lost most of its former momentum in our days (see chapter 5.5 and 5.6). BI 3010 H08 Population Genetics Halliburton Chapter 4-5

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25 BI 3010 H08 Population Genetics Halliburton Chapter 4-5 Two simulations of an eugenics program (PopG.exe screenshots): Even after 10 generations ( ~300 years), there's a fairly high frequency of the bad allele (and heterozygotes)